There is considerable recent interest in potential relationships between exposure to stressors and the functioning of the immune system. This is because alterations in immune function might mediate the impact of stressors on the development of diseases ranging from AIDS to cancer. Indeed, it has been argued that individual differences concerning the development and expression of AIDS symptoms from infection with HIV might be partially accounted for by the occurrence of psychological or physical stress at a critical stage in the cascade of immune reactions to the virus. This proposal focuses on in vivo changes in immune function. The specific aims of the proposal are: 1) To study behavioral factors which are important in determining whether and how stressor exposure will alter the formation of specific antibody (Ab) and Ab secreting cells (ASCs) to the antigen (Ag) KLH. Although there have been numerous demonstrations that exposure to painful or aversive events can alter some aspect of immune function, there has been very little analytic work directed at isolating important behavioral modulating factors. Here we wish to focus on 2 factors: a) Behavioral controllability of the stressor, both in the shock and defeat paradigms, b) Dominance. 2) To study neural and neuroendocrine mediators by which the stress conditions studied alter Ab levels. Focus is on 2 different but related issues. a) The central nervous system processes that mediate between the stressor and the peripheral changes that could contact immune organs and cells. Noradrenergic (NE) processes associated with the paraventricular nucleus (PVN) of the hypothalamus will receive particular attention. The PVN is a key structure in controlling both pituitary-adrenal and sympathoadrenomedullary activity, and the NE input to the PVN is a major stimulatory factor. b) The peripheral neuroendocrine mediators that are responsible for the stress-produced Ab changes. Here emphasis will be on elucidating the roles of adrenal corticosteroids and plasma catecholamines released by the adrenal medulla and sympathetic terminals. 3) To study immunologic changes produced by stressors and their neural and neuroendocrin sequelae that might be responsible for the reduced Ab formation, the focus will be on stressor produced alterations in cell trafficking between immune compartments, resulting in changed ratios of lymphocyte phenotypes.